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Am Fam Physician. 2014;89(2):136

Clinical Question

Do adults with type 2 diabetes mellitus who are treated with pioglitazone (Actos) have an increased risk of bladder cancer?

Bottom Line

This review of all available data found a significantly increased risk of bladder cancer among adults with type 2 diabetes treated with pioglitazone. Pioglitazone also significantly increases the risk of heart failure, and there is minimal, if any, patient-oriented evidence of benefit from treatment (Richter B, Bandeira-Echtler E, Bergerhoff K, Clar C, Ebrahim SH. Cochrane Database Syst Rev. 2006; [4]:CD006060). The French and German governments have suspended or strongly curtailed the use of pioglitazone. It lowers A1C levels, but I would not want my loved ones taking this stuff. (Level of Evidence = 2b)


Because of concern that pioglitazone is associated with an increased risk of bladder cancer, the French and German medicine agencies have suspended the use of pioglitazone or strongly advised physicians to stop prescribing it. The investigators thoroughly searched multiple databases (Medline, Embase, the Cochrane Register, the U.S. Food and Drug Administration web-site, and, reviewed bibliographic references of relevant articles, and contacted known researchers for longitudinal studies of patients who had type 2 diabetes with or without exposure to pioglitazone. Two authors independently performed the search and evaluated the methodologic rigor and the eligibility of individual trials. Disagreements were resolved by consensus discussion with a third reviewer. Observational and experimental trials were included, and sensitivity analyses were performed to assess the effect of study design and quality.

Six articles (N = 215,142) met inclusion criteria, including one large randomized controlled trial, one prospective cohort study, and four retrospective studies. The retrospective studies included reports from large population-based databases, including the French health care system, Kaiser Permanente Northern California, the Taiwanese national health system, and the United Kingdom general practice research database. Follow-up occurred for a median of 44 months. Compared with the nonexposed group, bladder cancer occurred significantly more often among patients exposed to pioglitazone (hazard ratio = 1.23; 95% confidence interval, 1.09 to 1.39; number needed to treat to harm = 20,903). The risk of bladder cancer was significantly increased with longer duration of pioglitazone use but not with increasing cumulative dosage.

Study design: Systematic review

Funding source: Self-funded or unfunded

Setting: Various (meta-analysis)

Reference: FerwanaMFirwanaBHasanRet alPioglitazone and risk of bladder cancer: a meta-analysis of controlled studies. Diabet Med.2013; 30( 9): 1026– 1032.

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